BCMA-targeted therapy enables combined haploidentical stem cell and kidney transplantation in a highly sensitized...

A 64-year-old woman with multiple myeloma and end-stage kidney disease was initially deemed ineligible for combined haploidentical hematopoietic stem cell and kidney transplantation due to positive flow cytometry crossmatch from high levels of donor-specific antihuman leukocyte antigen antibodies (DSA). She was treated with elranatamab, a B cell maturation antigen-directed CD3 bispecific T cell engager, which induced a deeper myeloma remission and led to a marked reduction in DSAs. Her calculated panel reactive antibodies decreased significantly from 97% to 24%. Once DSA levels fell below 1,000 mean fluorescence intensity, she underwent conditioning and proceeded to a successful combined haploidentical peripheral blood stem cell and kidney transplantation. The transplant course was favorable, resulting in full donor chimerism and excellent renal function at 1 year posttransplant, without major infectious complications. Posttransplant immunosuppression for graft-versus-host disease prophylaxis was gradually tapered off to complete discontinuation. Elranatamab therapy was then continued until 1 year posttransplant to reduce the risk of myeloma relapse. This case demonstrates that B cell maturation antigen-targeted therapy can serve as an effective desensitization strategy, enabling transplantation in highly sensitized patients who would otherwise have limited treatment options.